Biology subjects

Ridge, P. G.

Publications and source records attributed to Ridge, P. G..

8 recordsLinked to original sources

bioRxiv2025

Ramp sequence may explain synonymous variant association with Alzheimer's disease in the Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRA)

BACKGROUNDSynonymous variant NC_000007.14:g.100373690T>C (rs2405442:T>C) in the Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRA) gene was previously associated with decreased risk for Alzheimers disease (AD) in genome-wide association studies, but its biological impact is largely unknown. OBJECTIVEWe hypothesized that rs2405442:T>C decreases mRNA and protein levels by destroying a ramp of slowly translated codons at the 5 end of PILRA. METHODSWe assessed rs2405442:T>C predicted effects on PILRA through quantitative polymerase chain reactions (qPCR) and enzyme-linked immunosorbent assays (ELISA) using Chinese hamster ovary (CHO) cells. RESULTSBoth mRNA (P=1.9184 x 10-13) and protein (P=0.01296) levels significantly decreased in the mutant versus the wildtype in the direction that we predicted based on destroying a ramp sequence. CONCLUSIONSWe show that rs2405442:T>C alone directly impacts PILRA mRNA and protein expression, and ramp sequences may play a role in regulating AD-associated genes without modifying the protein product. Research in ContextO_LISystematic review: Genetic variants identified through genome-wide association studies often lack biological support for their association with Alzheimers disease. Although synonymous variant rs2405442:T>C in PILRA was previously reported as protective against Alzheimers disease, its effects have generally been attributed to linkage with missense variant, rs1859788:A>G. C_LIO_LIInterpretation: We show that rs2405442:T>C alone decreases mRNA and protein levels by destroying a ramp of slowly translated codons at the beginning of PILRA. We also show that a ramp sequence is present in PILRA and likely regulates mRNA and protein levels, thus offering a plausible biological mechanism explaining rs2405442:T>C association with Alzheimers disease independent of rs1859788:A>G. C_LIO_LIFuture directions: We provide the first protocol to evaluate how disease-associated variants impact ramp sequences, which could explain why some genetic variants are reported by genome-wide association studies. Future studies might examine if the ramp sequence could be therapeutically targeted to regulate PILRA expression without changing the protein product. C_LI

genetics↗

bioRxiv2024

A Draft Pacific Ancestry Pangenome Reference

Individuals of Pacific ancestry suffer some of the highest rates of health disparities yet remain vastly underrepresented in genomic research, including currently available linear and pangenome references. To begin addressing this, we developed the first Pacific ancestry pangenome reference using 23 individuals with diverse Pacific ancestry. We assembled 46 haploid genomes from these 23 individuals, resulting in highly accurate and contiguous genome assemblies with an average quality value of 55.0 and an average N50 of 40.7 Mb, marking the first de novo assembly of highly accurate Pacific ancestry genomes. We combined these assemblies to create a pangenome reference, which added 30.6 Mb of novel sequence missing from the Human Pangenome Reference Consortium (HPRC) reference. Mapping short reads to this pangenome reduced variant call errors and yielded more true-positive variants compared to the HPRC and T2T-CHM13 references. This Pacific ancestry pangenome reference serves as a resource to enhance genetic analyses for this underserved population.

genomics↗

bioRxiv2021

Genome of a Giant (Trevally): Caranx ignobilis

Caranx ignobilis, commonly known as the kingfish or giant trevally, is a large, reef-associated apex predator. It is a prized sportfish, targeted heavily throughout its tropical and subtropical range in the Indian and Pacific Oceans, and it has drawn significant interest in aquaculture due to an unusual tolerance for freshwater. In this study, we present a high-quality nuclear genome assembly of a C. ignobilis individual from Hawaiian waters, which have recently been shown to host a genetically distinct population. The assembly has a contig NG50 of 7.3Mbp and scaffold NG50 of 46.3Mbp. Twenty-five of the 203 scaffolds contain 90% of the genome. We also present the raw Pacific Biosciences continuous long-reads from which the assembly was created. A Hi-C dataset (Dovetail Genomics Omni-C) and Illumina-based RNA-seq from eight tissues are also presented; the latter of which can be particularly useful for annotation and studies of freshwater tolerance. Overall, this genome assembly and supporting data is a valuable tool for ecological and comparative genomics studies of kingfish and other carangoid fishes.

genomics↗

bioRxiv2021

Genome Assembly of the Roundjaw Bonefish (Albula glossodonta), a Vulnerable Circumtropical Sportfish

BackgroundBonefishes are cryptic species indiscriminately targeted by subsistence and recreational fisheries worldwide. The roundjaw bonefish, Albula glossodonta is the most widespread bonefish species in the Indo-Pacific and is listed as vulnerable to extinction by the IUCNs Red List due to anthropogenic activities. Whole-genome datasets allow for improved population and species delimitation, which - prior to this study - were lacking for Albula species. ResultsWe generated a high-quality genome assembly of an A. glossodonta individual from Hawai i, USA. The assembled contigs had an NG50 of 4.75 Mbp and a maximum length of 28.2 Mbp. Scaffolding yielded an NG50 of 14.49 Mbp, with the longest scaffold reaching 42.29 Mbp. Half the genome was contained in 20 scaffolds. The genome was annotated with 28.3 K protein-coding genes. We then analyzed 66 A. glossodonta individuals and 38,355 SNP loci to evaluate population genetic connectivity between six atolls in Seychelles and Mauritius in the Western Indian Ocean. We observed genetic homogeneity between atolls in Seychelles and evidence of reduced gene flow between Seychelles and Mauritius. The South Equatorial Current could be one mechanism limiting gene flow of A. glossodonta populations between Seychelles and Mauritius. ConclusionsQuantifying the spatial population structure of widespread fishery species such as bonefishes is necessary for effective transboundary management and conservation. This population genomic dataset mapped to a high-quality genome assembly allowed us to discern shallow population structure in a widespread species in the Western Indian Ocean. The genome assembly will be useful for addressing the taxonomic uncertainties of bonefishes globally.

genomics↗

bioRxiv2020

A Comprehensive Analysis of the Phylogenetic Signal in Ramp Sequences in 211 Vertebrates

BackgroundRamp sequences increase translational speed and accuracy when rare, slowly-translated codons are found at the beginnings of genes. Here, the results of the first analysis of ramp sequences in a phylogenetic construct are presented. MethodsRamp sequences were compared from 211 vertebrates (110 Mammalian and 101 non-mammalian). The presence and absence of ramp sequences was analyzed as a binary character in a parsimony and maximum likelihood framework. Additionally, ramp sequences were mapped to the Open Tree of Life taxonomy to determine the number of parallelisms and reversals that occurred, and these results were compared to what would be expected due to random chance. Lastly, aligned nucleotides in ramp sequences were compared to the rest of the sequence in order to examine possible differences in phylogenetic signal between these regions of the gene. ResultsParsimony and maximum likelihood analyses of the presence/absence of ramp sequences recovered phylogenies that are highly congruent with established phylogenies. Additionally, the retention index of ramp sequences is significantly higher than would be expected due to random chance (p-value = 0). A chi-square analysis of completely orthologous ramp sequences resulted in a p-value of approximately zero as compared to random chance. DiscussionRamp sequences recover comparable phylogenies as other phylogenomic methods. Although not all ramp sequences appear to have a phylogenetic signal, more ramp sequences track speciation than expected by random chance. Therefore, ramp sequences may be used in conjunction with other phylogenomic approaches.

evolutionary biology↗

bioRxiv2019

Codon Pairs are Phylogenetically Conserved: Codon pairing as a new class of phylogenetic characters

Identical codon pairing and co-tRNA codon pairing increase translational efficiency within genes when two codons that encode the same amino acid are located within a ribosomal window. By examining both identical and co-tRNA codon pairing across 23 423 species, we determined that both pairing techniques are phylogenetically informative across all domains of life using either an alignment-free or parsimony framework. We also determined that conserved codon pairing typically has a smaller window size than the length of a ribosome. We also analyzed frequencies of codon pairing for each codon to determine which codons are most likely to pair. The alignment-free method does not require orthologous gene annotations and recovers species relationships that are comparable to other alignment-free techniques. Parsimony generally recovers phylogenies that are more congruent with the established phylogenies than the alignment-free method. However, four of the ten taxonomic groups do not have sufficient ortholog annotations and are therefore recoverable using only the alignment-free methods. Since the recovered phylogenies using only codon pairing largely match established phylogenies and are comparable to other algorithms, we propose that codon pairing biases are phylogenetically conserved and should be considered in conjunction with current techniques in future phylogenomic studies. Furthermore, the phylogenetic conservation of codon pairing indicates that codon pairing plays a greater role in the speciation process than previously acknowledged.\n\nAvailabilityAll scripts used to recover and compare phylogenies, including documentation and test files, are freely available on GitHub at https://github.com/ridgelab/codon_pairing.

evolutionary biology↗

bioRxiv2019

Codon Use and Aversion is Largely Phylogenetically Conserved Across the Tree of Life

Using parsimony, we analyzed codon usages across 12 337 species and 25 727 orthologous genes to rank specific genes and codons according to their phylogenetic signal. We examined each codon within each ortholog to determine the codon usage for each species. In total, 890 814 codons were parsimony informative. Next, we compared species that used a codon with species that did not use the codon. We assessed each codons congruence with species relationships provided in the Open Tree of Life (OTL) and determined the statistical probability of observing these results by random chance. We determined that 25 771 codons had no parallelisms or reversals when mapped to the OTL. Codon usages from orthologous genes spanning many species were 1 109x more likely to be congruent with species relationships in the OTL than would be expected by random chance. Using the OTL as a reference, we show that codon usage is phylogenetically conserved within orthologous genes in archaea, bacteria, plants, mammals, and other vertebrates. We also show how to use our provided framework to test different tree hypotheses by confirming the placement of turtles as sister taxa to archosaurs.\n\nAvailabilityAll scripts, a README, and necessary test files are freely available on GitHub at https://github.com/ridgelab/codon_congruence\n\nContactperry.ridge@byu.edu

evolutionary biology↗

bioRxiv2019

Systematic analysis of dark and camouflaged genes: disease-relevant genes hiding in plain sight

BackgroundThe human genome contains dark gene regions that cannot be adequately assembled or aligned using standard short-read sequencing technologies, preventing researchers from identifying mutations within these gene regions that may be relevant to human disease. Here, we identify regions that are dark by depth (few mappable reads) and others that are camouflaged (ambiguous alignment), and we assess how well long-read technologies resolve these regions. We further present an algorithm to resolve most camouflaged regions (including in short-read data) and apply it to the Alzheimers Disease Sequencing Project (ADSP; 13142 samples), as a proof of principle.\n\nResultsBased on standard whole-genome lllumina sequencing data, we identified 37873 dark regions in 5857 gene bodies (3635 protein-coding) from pathways important to human health, development, and reproduction. Of the 5857 gene bodies, 494 (8.4%) were 100% dark (142 protein-coding) and 2046 (34.9%) were [≥]5% dark (628 protein-coding). Exactly 2757 dark regions were in protein-coding exons (CDS) across 744 genes. Long-read sequencing technologies from 10x Genomics, PacBio, and Oxford Nanopore Technologies reduced dark CDS regions to approximately 45.1%, 33.3%, and 18.2% respectively. Applying our algorithm to the ADSP, we rescued 4622 exonic variants from 501 camouflaged genes, including a rare, ten-nucleotide frameshift deletion in CR1, a top Alzheimers disease gene, found in only five ADSP cases and zero controls.\n\nConclusionsWhile we could not formally assess the CR1 frameshift mutation in Alzheimers disease (insufficient sample-size), we believe it merits investigating in a larger cohort. There remain thousands of potentially important genomic regions overlooked by short-read sequencing that are largely resolved by long-read technologies.

genomics↗